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A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial (PENS)

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ClinicalTrials.gov Identifier: NCT03350750
Recruitment Status : Recruiting
First Posted : November 22, 2017
Last Update Posted : June 7, 2018
Sponsor:
Collaborator:
University of Utah
Information provided by (Responsible Party):
Johns Hopkins University

November 14, 2017
November 22, 2017
June 7, 2018
May 21, 2018
November 2019   (Final data collection date for primary outcome measure)
Gait velocity [ Time Frame: 4 months from baseline ]
Evaluation of CSF shunting in INPH patients through a group comparison of improvement from baseline at four months between active and placebo-controlled groups, using the primary endpoint of gait velocity
Same as current
Complete list of historical versions of study NCT03350750 on ClinicalTrials.gov Archive Site
  • Gait velocity [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting, using the primary outcome of gait velocity.
  • Cognition using Montreal Cognitive Assessment (MoCA) [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using MoCA test to assess cognition
  • Cognition using Symbol Digit Modalities Test (SDMT) [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using SDMT to assess cognition
  • Function using Modified Rankin Scale (MRS) [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using MRS to assess function
  • Function using Lawton Activities of Daily Living/Independence in Activities of Daily Living (ADL/IADL) tests [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using ADL/IADL test to assess function
  • Bladder Control [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months using Overactive Bladder Questionnaire, short form (OAB-q sf.) to assess bladder control
  • Frequency of adverse events [ Time Frame: 4 months ]
    Evaluate the effect of shunting between active and placebo-controlled groups at four months by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated.
  • Cognition using MoCA [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using MoCA to assess cognition
  • Cognition using SDMT [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using SDMT to assess cognition
  • Function using MRS [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using MRS to assess function
  • Function using ADL/IADL [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using ADL/IADL to assess function
  • Bladder control [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting using OAB-q test to assess bladder control
  • Frequency of adverse effects [ Time Frame: 8 months ]
    Evaluate the clinical improvement of all study participants at eight months of active shunting by assessing the frequency of falls, surgical and non-surgical complications, related and unrelated.
  • Adverse events [ Time Frame: 4 and 8 months of active shunting ]
    Compare adverse events (AEs) in the active versus placebo-controlled group at four months and at eight months of active shunting.
Same as current
Not Provided
Not Provided
 
A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial
A Placebo-Controlled Effectiveness in INPH Shunting (PENS) Trial: Proof of Concept
The Placebo-Controlled Effectiveness in Idiopathic Normal Pressure Hydrocephalus (iNPH) Shunting (PENS) trial is a multi-center blinded, randomized, placebo-controlled design investigation of cerebrospinal fluid (CSF) shunt surgery to study the shunt effectiveness in iNPH patients.
The primary intervention will be setting the FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve to active (open shunt group)(setting 4)(110 mm H2O) or placebo (closed shunt group)(setting 8)(>400 mm H2O)in a 1:1 ratio. By the time of the primary objective evaluation at four months, the closed shunt group will have zero months of active treatment, and the open shunt group will have four months of active treatment. At four months, shunts for subjects in the closed shunt group will be adjusted to setting 4. To maintain blinding, all patients will be adjusted/ mock adjusted to the active setting in a similar fashion. Patients from both groups will not be adjusted before four months of active treatment, unless judged medically necessary by the treating team. Following four months of active treatment, all subjects in each group will have shunt adjustments according to clinical standards at each center.
Interventional
Not Applicable
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The primary intervention will be the initiation of the randomized initial shunt valve opening pressure setting to create a delayed treatment group in half of the study patients.

Randomization will be to active or placebo (closed) shunt settings. At the time of the standard four-month evaluation, all subjects will be similarly non-invasively adjusted to bring all subjects in both groups to the active setting while maintaining blinding of the subjects. All settings will be verified by the adjusting neurosurgeon.

Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Idiopathic Normal Pressure Hydrocephalus (INPH)
Device: programmable CSF shunt valve
Brain shunt surgery using a programmable CSF shunt valve
Other Name: FDA-approved Certas Plus with Siphonguard
  • Active Comparator: Open Shunt Group
    FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to active (open shunt group)(setting 4)(110 mm H2O) at time of shunt implantation
    Intervention: Device: programmable CSF shunt valve
  • Sham Comparator: Closed Shunt Group
    FDA-approved Certas Plus with Siphonguard, programmable CSF shunt valve setting to placebo (closed shunt group)(setting 8)(>400 mm H2O) at time of shunt implantation followed by setting to active (setting 4) (110 mm H2O) four months after the procedure.
    Intervention: Device: programmable CSF shunt valve
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
40
Same as current
November 2021
November 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Age ≥ 60 years; and
  • Diagnosis of INPH based on clinical criteria and testing as described in the INPH Guidelines;2 and
  • One positive supplementary test whether infusion test, large volume lumbar puncture (LP) or extended cerebrospinal fluid (CSF) drainage;3 and
  • Duration of gait impairment ≥ 6 months.

Exclusion Criteria:

  • Unable to walk 10 meters with or without an assistive device; or
  • Baseline gait velocity >1 m/sec. with or without an assistive device; or
  • Unable to return to the study center for follow up evaluation and shunt programming; or
  • Patient is not medically cleared for shunt surgery per local standards; or
  • Secondary NPH. (Prior encephalitis, meningitis, subarachnoid hemorrhage, traumatic brain injury (including concussion), brain abscess, brain tumor, obstructive hydrocephalus (including acquired aqueductal stenosis and carcinomatous meningitis)); or
  • Prior or existing shunts, endoscopic third ventriculostomy, or any previous surgical intervention for hydrocephalus; or
  • Previous intracranial neurosurgical procedure; or
  • Current treatment with anticoagulation medications or expected to be on anticoagulation medications in future based on clinician evaluation; or
  • Large cerebral or cerebellar infarction (asymptomatic lacunar infarctions are permitted); or
  • Hemiparesis, cerebellar signs or neurological deficits (e.g., cervical or lumbar myelopathy, previous stroke) precluding gait assessment; or
  • Diagnosis of Parkinsons disease; or
  • Diagnosed clinical depression; or
  • Diagnosis of schizophrenia or any psychiatric diagnosis which in the clinician's judgment will complicate the outcome evaluation; or
  • Sensory or functional deficit (e.g., uncorrectable severe visual or hearing impairment) that does not allow full clinical evaluation; or
  • Dementia, documented with a Montreal Cognitive Assessment (MoCA) score of 21 or less, taken at standard initial evaluation; or
  • Conditions impairing gait that are considered to be unrelated to hydrocephalus, such as hemiparesis, spasticity, cerebellar ataxia or musculoskeletal and joint disease.
Sexes Eligible for Study: All
60 Years and older   (Adult, Older Adult)
No
Contact: Lynn Smith 4106148142 lsmith36@jhmi.edu
Canada,   Sweden,   United States
 
 
NCT03350750
IRB00083576
Yes
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Pediatric Postmarket Surveillance of a Device Product: No
Product Manufactured in and Exported from the U.S.: No
Plan to Share IPD: Yes
Plan Description:

After subject enrollment and follow up have been completed, the Data Coordinating Center (DCC) of the study will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be re-coded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers.

The DCC will also prepare a data dictionary that provides a concise definition of every data element included in the database. If specific data elements have idiosyncrasies that might affect interpretation or analysis, this will be discussed in the dictionary document.

In accordance with policies determined by the investigators and funding sponsors, the releasable database will be provided to users in electronic form.

Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Time Frame: One year after publication of the results of the primary analysis.
Access Criteria: individual participant data (IPD) will be made available to researchers submitting a request for data that includes an analytic plan approved by the Institutional Review Board (IRB) at their institution
Johns Hopkins University
Johns Hopkins University
University of Utah
Principal Investigator: Mark Luciano, MD Johns Hopkins University
Johns Hopkins University
June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP